The Influence Of Epidermal Growth Factor Receptor Inhibitor In Combination With Chemotherapeutics On Proliferation And Apoptosis In Human Gastric Cancer Cells

Objective: To investigate the influence of epidermal growth factorreceptor inhibitor, Erlotinib (Tarceva^TM, OSI-774), given alone or incombination with chemotherapeutics (5-Fluorouracil or Paclitaxel) onproliferation and apoptosis in SNU-1 human gastric cancer cells.Methods: Erlotinib (Tarceva^TM, OSI-774) was given alone or as a doubletwith 5-fluorouracil (5-Fu) or paclitaxel (PTX) in SNU-1 human gastriccancer cells. The inhibition of proliferation was analyzed with MTT assay.The interaction between Edotinib and 5-Fu/PTX was analyzed bycombination index (CI). Gastric cancer cells were double stained withAnnexin-V and propidium iodide (PI), then flow cytometric analysis wasused to detect the apoptosis of the gastric cancer cells. Western blottingwas used to analyze poly(ADP-ribose) polymerase (PARP) cleavages.Results: Erlotinib alone or in combination with 5-Fu/PTX inhibits thegrowth of SNU-1 gastric cancer cells concentration-dependently andtime-dependently. According to CI of Edotinib+PTX＜CI ofErlotinib+5-Fu＜0.8, these data indicate that Edotinib in combinationwith 5-Fu/PTX synergistically inhibits the growth of SNU-1 cells andsynergism of Erlotinib+PTX is greater than that of Erlotinib+5-Fu. Flow cytometric analysis of SNU-1 cells exposed to 50μmol/L of Erlotinib,15μmol/L of 5-Fu or 0.5μmol/L of PTX for 72h showed that the apoptoticrate of these three groups is 23.2%±3.1%,39.7%±3.5% and 56.6%±4.1%respectively, which is higher than that of control group (7.6%±1.2%)significantly (P＜0.05). Apoptotic rates of combination groups(49.1%±2.7% for Erlotinib+5-Fu and 62.7%±4.3% for Erlotinib+PTX)were higher than those of single drug groups (P＜0.05). PARPcleavages in SNU-1 cells exposed to Erlotinib or a doublet of Erlotiniband 5-Fu/PTX were more than those of control group.Conclusion: When Erlotinib is given alone or as a doublet with 5-Fu orPTX, its antitumor effects are concentration-dependent andtime-dependent. Erlotinib induces apoptosis in gastric cancer cells bypromoting the cleavage of PARE Erlotinib in combination with 5-Fu orPTX has synergistic antitumor effects and synergism of Edotinib+PTX isgreater than that of Erlotinib+5-Fu.